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Biochem 2 - Final > Cysteine Article Takeaways > Flashcards

Cysteine Article Takeaways Flashcards

0
Q

Tons of toxic industrial waste products, including heavy metals are being mixed with what, being dispersed across America’s farmland.

A

liquid agricultural fertilizers

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1
Q

We are all vulnerable to what type of exposure to toxic metals?

A

Chronic, low level exposure

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2
Q

What are the heavy metals that are controversially put in fertilizers, soil, and pastures?

A

Aresenic, lead, cadmium, nickel, mercury, and uranium

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3
Q

How can acute metal toxicities be diagnosed?

A

Patient history and overt symptoms

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4
Q

Chronic, low-level exposure to heavy metals produces what type of symptoms? When do these symptoms tend to be expressed?

A

non-descript symptoms; overt expression of physiological aberrations are often not realized until later in life

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5
Q

Among the most insidious toxic metals are the sulfhydryl-reactive metals, which include which 4 metals?

A
  • mercury (Hg)
  • cadmium (Cd)
  • lead (Pb)
  • arsenic (As)
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6
Q

Which two metals are heavily deposited in the kidney?

A

Mercury (Hg) and Cadmium (Cd)

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7
Q

What is the biological half-life of cadmium (Cd) in the kidney?

A

On the order of decades

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8
Q

Which metal does not readily cross the BBB in adults, unlike mercury (Hg)?

A

Cadmium (Cd)

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9
Q

Which metal is associated more with peripheral neuropathy than with disorders of the CNS?

A

Cadmium (Cd)

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10
Q

Which metal is deposited primarily in bone?

A

Lead (Pb)

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11
Q

Which metal disrupts erythropoiesis?

A

Lead (Pb)

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12
Q

Which chronic conditions are associated with heavy metal toxicity? (list of symptoms)

A

fatigue, musculoskeletal pain, neurological disorders, depression, poor cognitive function, poor memory, and allergic hypersensitivity.

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13
Q

Which metal is the most volatile over the other sulfhydryl-reactive metals?

A

Mercury (Hg)

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14
Q

What is the primary source of chronic, low levels of Mercury (Hg) exposure?

A

Dental amalgams and fish

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15
Q

What are two ways in which mercury enters water to pollute fish?

A

Off-gassing from the earth’s crust and industrial pollution

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16
Q

How does mercury make its way up the food chain?

A

It is methylated by algae and bacteria in water and moves up the food chain

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17
Q

Which fish contain the highest concentrations of mercury?

A

swordfish, shark, salmon, and tuna

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18
Q

What are other sources of mercury (aside from off-gassing and pollution)?

A

combustion of fossil fuels, production of chlorine, paper and pulp, fungicides/seed preservatives, and some paints
(in some parts of the world, large amounts of Hg enter the environment as a result of careless processing of gold from ore)

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19
Q

What are the two major, highly absorbed subspecies of mercury?

A

Elemental Hg and methylmercury (MeHg)

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20
Q

What type and percentage of mercury is found in “silver” dental amalgams?

A

50% Elemental mercury

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21
Q

Elemental mercury is volatile and does what at room temperature?

A

vaporizes

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22
Q

Mercury is poorly absorbed if ingested, but is efficiently absorbed through which organ and means? What important barrier is crossed?

A

Lungs/respiration; blood brain barrier

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23
Q

Due to its lipophilic nature, elemental mercury has a high affinity for which membranes?

A

Myelin and lipid membranes

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24
Q

Once inside the cell, elemental mercury undergoes which reaction to become reactive Hg2+?

A

Elemental Hg is oxidized by catalase

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25
Q

MeHg, derived from fish and dimethylmercury is readily absorbed in what area?

A

gastrointestinal tract

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26
Q

MeHg can be de-methylated and oxidized into which form?

A

Hg2+

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27
Q

Once assimilated in the cell, Hg2+ and MeHg+ form covalent bonds with which two residues of proteins?

A

glutathione and cysteine

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28
Q

Once absorbed, Hg has a _____ excretion rate.

A

Low

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29
Q

A significant proportion of assimilated Hg is retained and continually accumulates in which 3 areas?

A

kidneys, neurological tissue, and the liver

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30
Q

Upon autopsy, high levels of mercury have been found in which tissues of dentists?

A

cardiac, thyroid, pituitary

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31
Q

The sulfhydryl-reactive metals have three major properties: the first is that transition metals promote what?

A

hydrogen peroxide and enhance the subsequent iron- and copper-induced production of lipid peroxides and the highly reactive hydroxylradical.

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32
Q

Which products alter membrane structure and are highly disruptive of mitochondrial function?

A

lipid peroxides

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33
Q

The pro-oxidant properties of the sulfhydryl-reactive metals is exacerbated by what effects on antioxidant processes?

A

inhibitory

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34
Q

Which two metals have a high affinity for glutathione (GSH)?

A

Mercury (Hg) and Cadmium (Cd)

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35
Q

A single atom of CD or Hg can bind to and cause irreversible excretion of what?

A

up to two GSH tripeptides

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36
Q

The metal-GSH conjugation process is desirable because of which result?

A

excretion of the toxic metal into the bile

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37
Q

The metal-GSH conjugation process is detrimental because it…

A

depletes the cell of GSH and thus decreases antioxidant capacity

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38
Q

Which two enzymes, related to GSH are inhibited by mercury?

A

GSH synthetase and GSH reductase

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39
Q

Mercury also inhibits the activities of the free radical quenching enzymes:

A

Catalase, superoxide dismutase, and GSH peroxidase

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40
Q

Inhibition of GSH peroxidase has been attributed to the formation of which complex?

A

mercury-selenide complex

41
Q

In addition to promoting lipid peroxidation, depleting GSH and inhibiting antioxidative processes the sulfhydryl-reactive-metals disrupt the structure and function of numerous important protein through which means?

A

direct binding to free sulfhydryl groups.

42
Q

Metal induced inhibition of Na/K/ATPase can result in what problems with astrocytes?

A

Swelling and destruction

43
Q

What are the primary functions of astrocytes in the CNS?

A

homeostatic regulation of synaptic pH, Na/K and glutamate and metal sequestration

44
Q

Mercury inhibits the polymerization of _________ causing the depolymerization of existing microtubules.

A

tubulin

45
Q

Based on the study, short term and long term exposure to MeHg in drinking water resulted in a two- to three-fold up-regulation of what?

A

mRNA encoding for y-glutamyclcysteine synthetase (which is the rate limiting enzyme in GSH synthesis)

46
Q

Which 3 metal toxicities cause fatigue?

A

Mercury, Lead, and Cadmium

47
Q

Which metal toxicity does not cause fatigue?

A

Arsenic

48
Q

Which metal toxicity causes depression?

A

Mercury

49
Q

Which 2 metal toxicities lead to poor memory?

A

Mercury and lead

50
Q

Which metal toxicity has negative effects on cognitive function?

A

Mercury

51
Q

Which metal toxicity leads to emotional instability?

A

Mercury

52
Q

Which metal toxicity leads to peripheral numbness or tingling?

A

Mercury

53
Q

Which metal toxicity decreases senses of touch?

A

Mercury

54
Q

Which metal toxicity causes hearing or vision loss?

A

Mercury

55
Q

Which metal toxicity is responsible for hypersensitivities and allergies?

A

Mercury

56
Q

Which heavy metal toxicity causes persistent infections, including chronic yeast overgrowth?

A

Mercury

57
Q

Which heavy metal causes compromised immune function?

A

Mercury

58
Q

Which metal toxicity causes cardiovascular disease?

A

Mercury

59
Q

Which metal toxicity causes loss of apetite?

A

Lead

60
Q

Which metal toxicity causes headaches?

A

Lead

61
Q

Which metal toxicity leads to an inability to concentrate?

A

Lead

62
Q

Which metal toxicity causes ADD/ADHD?

A

Lead

63
Q

Which metal toxicity causes aberrant behavior?

A

Lead

64
Q

Which metal toxicity causes decreased coordination?

A

Lead

65
Q

Which metal toxicity causes irritability?

A

Lead

66
Q

Which metal toxicity causes pain in the abdomen?

A

Lead

67
Q

Which metal toxicity causes pain in the bones and muscles?

A

Lead

68
Q

Which metal toxicity causes gout?

A

Lead

69
Q

Which 2 metal toxicities causes anemia?

A

Lead and Cadmium

70
Q

Which metal toxicity causes hypertension?

A

Cadmium

71
Q

Which metal toxicity causes muscle and joint pain?

A

Cadmium

72
Q

Which metal toxicity causes osteomalacia?

A

Cadmium

73
Q

Which metal toxicity causes lumbar pain?

A

Cadmium

74
Q

Which metal toxicity causes atherosclerosis?

A

Cadmium

75
Q

Which metal toxicity causes kidney damage with associated urinary loss of essential minerals, amino acids, and protein?

A

Cadmium

76
Q

Which metal toxicity causes malaise?

A

Arsenic

77
Q

Which metal toxicity causes muscle weakness?

A

Arsenic

78
Q

Which metal toxicity causes eczema?

A

Arsenic

79
Q

Which metal toxicity causes dermatitis?

A

Arsenic

80
Q

Which metal toxicity causes increased salivation and strong “garlic” breath?

A

Arsenic

81
Q

Why is Hg relative more neurotoxic than nephrotoxic?

A

Activities of GSSH reductase and GSH peroxidase increase in steady state levels producing a protective and adaptive response in the renal epithelial cells, whereas neurons do not have this adaptive capacity.

82
Q

Metallothioneins are a group of low molecular weight, intracellular proteins that serve as a storage depot for which 2 metals? What do they do?

A

Copper and zinc; “scavenge” sulfhydryl-reactive metals that enter the cell.

83
Q

Metallothioneins are rich in which amino acid? (~30%) Which heavy metal do they have a higher affinity for than zinc?

A

Cysteine; Hg and Cd

84
Q

Which amino acid inhibits transport of the MeHg-cysteine complex across the blood brain barrier?

A

L-Leucine

85
Q

Which other amino acids (aside from leucine) compete for the L-amino acid transport system?

A

valine, isoleucine, phenylalanine, tyrosine, and tryptophan

86
Q

Why would treatment with whey protein be helpful for heavy metal toxicity? (Whey protein contains 2.5 - 3% cysteine and 22-25% BCAAs)

A

Cysteine supports intracellular GSH production and metallothionein synthesis, yet provides adequate leucine to minimize the transport of metals into the CNS.

87
Q

True/False: Pharmacological doses of cysteine/NAC (in the range of 1500mg/daily) can potentially exacerbate the adverse neurological effects of toxic materials.

A

True

88
Q

Exposure to what metal directly affects uptake and release of dopamine, norepinephrine, and serotonin.

A

Mercury

89
Q

What is the indirect effect of Hg regarding neurotransmitters?

A

depletion or poor assimilation of specific amino acids which are precursors of neurotransmitters.

90
Q

Persistant candidiasis/dysbiosis associated with which metal burden can compromise the absorption of aromatic amino acids (phenylalanine/tyrosine/tryptophan) which are the precursors to dopamine/norepinephrine/serotonin respectively.

A

Mercury

91
Q

Metal-induced inhibition of the 5’deiodinase enzyme is related to general peroxidative effects through the inhibition of which metal?

A

Mercury

92
Q

HG is known to irreversibly bind to and “waste” which metal? Why does this matter?

A

selenium; 5’deiodinase is a selenium-dependent enzyme

93
Q

Which metal may inhibit the conversion of prohormone T4 to T3 by interfering with selenium availability?

A

Mercury

94
Q

How does mercury interfere with progesterone?

A

Hg binds to a free sulfhydryl group on the progesterone receptor and may thereby diminish progesterone binding and cellular response.

95
Q

What are the 2 links of Hg to chronic fatigue?

A
  • disruption in hormone metabolism (progesterone)

- binding to lipoic acid making lipoic acid unavailable for its vital role in the energy producing tricarboxylic acid

96
Q

Which two metals are readily displaced from metallothionein by Hg and Cd? For what are they co-factors?

A

Copper and zinc; superoxide dismutase and copper is required for the synthesis of the catecholamines

97
Q

Which metal is critical for wound healing, immune function, and metabolism of protein and nucleic acids?

A

Zinc

98
Q

Ethylenediamine tetraacetic acid (EDTA) and the dithiol complexing agents have affinities for which metals?

A

Cu, Zn, Mn, Cr, and Mo, and can indirectly result in Mg depletion

99
Q

What percentage of DMSA (a metal detoxification agent) absorbed is excreted in the urine as a cysteine-DMSA-cysteine disulfide complex?

A

90%; it would therefore be important to replace cysteine if using oral DMSA

Biochem 2 - Final (7 decks)

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